Exploring the Role of Genetics in Mental and Psychiatric Disorders

Mental and psychiatric disorders are a public health concern that continues to see research and investigation, and is still not fully understood. It is a growing and significant issue, which affects millions worldwide, across all ages and demographics. The causes and underlying mechanisms of these disorders have been studied extensively, and although the development of such disorders depends on multiple related and unrelated factors, recent research and studies have shown that, among the factors, genetics play a critical role. Throughout history, mental health has been an ill-understood concept. Those that suffered from the diseases were historically horribly mistreated, from PTSD-stricken soldiers in the First World War being shot for cowardice, to those with psychiatric and developmental disorders being lobotomized, permanently being reduced to a childlike and vegetative state. Fortunately, as our understanding of the mind has improved through advancements in research, especially since the mid-20th century, we have come to convincing evidence behind the role of genetics in the manifestation of disorders in people. Research has even suggested that disorders like depression, anxiety, schizophrenia, bipolar, and others are related in their genetic loci in humans. Such disorders, which cause pain and suffering to millions, could potentially be cured with further development and research. It is because of this that examining the causes of these disorders is important.

The role of genetics in mental and psychiatric disorders has been investigated in a study by Haney Gandal and other researchers, in which they highlight the importance of the understanding of genetic and environmental mechanisms that influence the development of psychiatric disorders. In this study, 700 samples from postmortem brains are analyzed and compared to control samples. The researchers also performed a genome-wide association study (GWAS, involving the rapid scanning of markers across complete sets of DNA/genomes of many people) to identify genetic variations usually found in those that suffer from the disorders.  The authors write that “the results suggest that there are important overlaps in the genetic and molecular mechanisms underlying seemingly distinct psychiatric disorders” (Gandal et al., 2018, p. 693), such as autism, bipolar disorder, depressive disorder, schizophrenia, and alcoholism, which most would view as distinct. Common genetic codes and traits within people that suffer from these disorders indicate that there are common genetic characteristics that influence the development of these disorders, confirming the role of genetics. Based on this, the study has suggested that a substantial proportion of the genetic risk for psychiatric disorders can be credited to common genetic variations. The authors further state, “these findings support the notion that many psychiatric disorders are genetically related and suggest that current nosology does not accurately reflect the true nature of underlying pathophysiology” (p. 693). Here, the authors are stating that the studied psychiatric disorders are shown to have genetic links, and that the current classifications and approaches to these diseases found in the medical world can no longer be considered correct or appropriate, based on the findings of the study. As such, the study of genetics and its roles in psychiatric disorders is important not only because it improves understanding, but also because this information is very important for possible methods of treatment and even prevention. Given the fact that genetic engineering and modification are becoming increasingly studied and closer to being applied, the fact that the “the gene expression patterns of ASD [autism], SCZ [schizophrenia], and BD [bipolar disorder] brains are more similar to each other than to controls” (p. 695) means that treatment is possible, and the effects of these disorders can be mitigated or even possibly removed.

The role of genetics in mental disorders has again been proven by another article, by Daly Sullivan and Michael O’Donovan. This article discusses and provides a comprehensive review of recent advances in genetic research, including the already mentioned use of genome-wide association studies (GWAS) to identify common genetic variants found in individuals with the disorders. According to the authors, “the picture emerging from genetic studies is one of highly polygenic disorders, with many common alleles of small effect contributing to risk” (p. 538). Essentially, the authors state that the disorders, while genetic, are far more complex than originally thought. They state that searching for specific “risk genes” may not be helpful in studying the diseases, because they are polygenic. In other words, they are caused by many small genes that, individually, do not produce a large enough effect on the phenotype (in this case, the expression of the disorder) to be observed. However, these smaller genes can have combined effects which can influence the expression or manifestation of the disorder. While the complicated nature of the disorders makes the finding of common factors difficult, the results still suggest that these disorders still share major commonalities in their genetic and molecular mechanisms. According to the authors, “heritability estimates suggest that genetics explains between 30% and 80% of the variance in liability to major psychiatric disorders” (p. 538), or, in other words, genetics accounts for between 30% and 80% of the variance in the chance to develop the major psychiatric disorders through inheritance. This is confirmed by other sources and specific examples, like in the case with bipolar disorder. Bipolar disorder is one of the most heritable diseases, and has considerable effects on a person’s energy, emotions, focus and concentration, and activity. This disease, according to the Black Dog Institute, holds high chances of heritability, and like other sources, states that genetic factors are around 80% of the determining factors in the development of bipolar disorder. According to the source, “if both parents have bipolar disorder, the likelihood of their child developing bipolar disorder rises to 40%” (lines 22-23). Disorders, therefore, clearly have genetic components that play a large role. Though the factors are not entirely genetics (with environment, illnesses, and experiences playing a role), and though not all disorders may be as heritable as bipolar disorder, the evidence found here makes a strong case for genetics being an important factor in the manifestation of these disorders.

Though some disorders, like autism and bipolar may be the most obvious cases for heritable and therefore genetics-related disorders, PTSD is another disorder which may have significant heritability, according to neuroscientist Jordan Smoller. In their article, “The Genetics of Stress-related Disorders: PTSD, Depression, and Anxiety Disorders”, Smoller provides an overview of the genetics of stress-related disorders. Smoller highlights that there is strong evidence supporting the genetic contribution to these conditions. According to him, “there is growing evidence that genetic factors interact with environmental factors, including traumatic life events and stress, to increase risk for stress-related disorders” (p. 299). In this quote, the author is explaining that other factors also influence the expression of disorders, including life experiences, stress, and the environment in which a person lives their life. However, a major factor still is genetics, and Smoller writes that disorders like PTSD, depression, and anxiety have “heritability estimates ranging from 30% to 70%” (p. 297), reaffirming the role of genetics. What is most surprising is that these disorders are not typically thought to be heritable and that they are produced purely from the experiences and environment of a person. As a result, the evidence that the author brings to the reader further proves that even disorders not associated to bipolar or autism have genetic components to them. Because of the genetic components of these diseases and the fact that they also interact with environmental factors, the author notes that research in this area could eventually lead the way to treatments for these disorders. This is especially interesting because previously, such disorders have traditionally been treated or mitigated through psychotherapy and less directly medical means. Nevertheless, as backed up by other sources, these disorders are highly complex and are also polygenic, but this still means that they are significantly influenced by genetics, confirming its role in these disorders. This topic is also explored by the University of San Diego, which, in a similar investigation, determined that “PTSD’s heritability — the level of influence genetics has on the variability of PTSD risk in the population — is between five and 20 percent” (paras. 11), and that PTSD, compared with 235 other disorders, shares “significant overlap with 21, including depression, schizophrenia, neuroticism, insomnia, asthma and coronary artery disease” (paras. 12). In these studies, genome-wide association studies (GWAS) are again employed to locate genetic similarities between those that suffer from the investigated disorders. Once again, genetic commonalities have been located, even to diseases that are not mental or psychiatric in nature (as demonstrated by overlaps with coronary artery disease).

A final study proving the relationship between genetics and psychiatric disorders is a genome-wide association study (GWAS) conducted by Phil Hyoun Lee and associated authors. In their study, the authors investigated the genetic relationships between ADHD, autism spectrum disorder, bipolar disorder, depressive disorder, OCD, schizophrenia, Tourette syndrome, and anorexia nervosa. Using a GWAS analyzing the genomes of over one million individuals (with and without disorders) from the Psychiatric Genomics Consortium and UK Biobank, the researchers reported “109 independent genome-wide significant loci associated with at least one of the eight disorders” (p. 1469). This suggests substantial genetic contributions not only to individual diseases, but the aforementioned array. Research has also exposed the role of shared genetic “pathways involved in neural development, synaptic function, and immune system regulation” (p. 1479). This means that they share biological mechanisms, also related to genetics. Additionally, as with other sources, Lee and the other authors have confirmed the polygenic nature of these psychiatric disorders, revealing that there is no single gene responsible for the manifestation of any given disorder. Rather, multiple genetic and environmental factors with individually small effects interact and contribute to the risk of developing these disorders.  The most overlap between disorders was observed “particularly between schizophrenia, bipolar disorder, and depression” (p. 1480). Once again, this proves these disorders are all related to each other in their genetic codes, and that they have more in common than would meet the eye. As such, the authors emphasize the importance of increased research, so that these disorders can be understood better, thus improving methods of diagnosis and treatment.

In conclusion, mental and psychiatric disorders are horrible conditions. Varied as they may be in the effects they cause in humans, many, based on research and genomic analysis, share common genetic coding and characteristics, as proven by multiple genome-wide association studies, in which up to a million people have been analyzed for common genomic features in those with these disorders. Many of these disorders are also heritable, something that is only possible through genetics. Though these disorders are highly complex and polygenic, they nonetheless share common biological mechanisms and genetic codes which are important to understand, so that better prevention and treatment strategies can be developed. Additionally, it cannot be overlooked that environment, lifestyle, and experiences also play a role in certain disorders. However, these ultimately interact with and combine with genetic factors to influence disorder development in people. Psychiatric disorders are a widespread and pervasive health issue that our modern society faces. They can have a significant impact on individuals, families, and entire societies, and an improved understanding of these disorders, especially their genetic components and causes, can be instrumental in mitigating and possibly even curing these disorders.

Works cited:

Black Dog Institute. (2022, January 31). Causes of bipolar disorder. Black Dog Institute. Retrieved April 28, 2023, from https://www.blackdoginstitute.org.au/resources-support/bipolar-disorder/causes/#:~:text=Bipolar%20disorder%20is%20the%20most,bipolar%20disorder%20rises%20to%2040%25.

Buschman, H. (2019, October 8). Large study reveals PTSD has strong genetic component like other psychiatric disorders. UC San Diego Health. https://health.ucsd.edu/news/press-releases/2019-10-08-study-reveals-ptsd-has-strong-genetic-component/

Gandal, Haney, J. R., Parikshak, N. N., Leppa, V., Ramaswami, G., Hartl, C., Schork, A. J., Appadurai, V., Buil, A., Werge, T. M., Liu, C., White, K. P., Horvath, S., & Geschwind, D. H. (2018). Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science (American Association for the Advancement of Science), 359(6376), 693–697. https://doi.org/10.1126/science.aad6469

Lee, P. H., Anttila, V., Won, H., Feng, Y.-C. A., Rosenthal, J., Zhu, Z., Tucker-Drob, E. M., Nivard, M. G., Grotzinger, A. D., Wang, J. C., Patel, K., Muntané, G., Adams, M. J., Blanchard, M. M., Brown, A., Carlin, J. B., Chen, C.-Y., Chesi, A., … Dale, A. M. (2019). Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell, 179(7), 1469–1482.e11. https://doi.org/10.1016/j.cell.2019.11.020

Smoller, J. W. (2016). The genetics of stress-related disorders: PTSD, depression, and anxiety disorders. Neuropsychopharmacology, 41(1), 297–319. https://doi.org/10.1038/npp.2015.266

SULLIVAN, DALY, M. J., & O’DONOVAN, M. (2012). Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nature Reviews. Genetics, 13(8), 537–551. https://doi.org/10.1038/nrg3240